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Control Of Transforming Growth Factor Beta In Airway Remodeling In The Role And Mechanism Of Airway Reconstruction

Posted on:2002-07-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:W W FanFull Text:PDF
GTID:1114360032452501Subject:Internal medicine
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Airway remodelling is a gradual pathological process in chronic obstructive pulmonary disease(COPD) and bronchial asthma. The mechanism of air~vay remodelling has not been clear.It has been known that a lot of factors that include bacteria.ximis.allergy or the harmful gas like smoke participate in the process.And it is also known that many kinds of cells or cytokines play an important role in the process. The main changes of airway remodelling are subepitheial fibrosis,tliickemng of smooth muscle and deposit of extracellar matrix that result in obstructive airflow with different degree,that shape pathological transform.And that increase the difficulty to cure it.The earlier opinion is that it is no way to reverse the airway remodelling and cure when it has formed. It has been reported that transforming growth factor-beta (TGF-. P.) play the role of many fibrosis disease such as hepatic fibrosis and it is one of the most grievous factors that result in fibrosis.Study has indicated that SaIvia Multiorrhiza can resist the process of hepatie fibrosis. In this report, a serial studies about the relationship of TGF- P with airway remodelling inodeland primary culture cell of lung fibroblast and the effect on experimental prevention or therapy on ariwav remodelling and their potential mechanisms were carried out. This research includes three parts. Firstiv.two model of arway remodelling in COPD and bronchial asthma was established and many kinds of celh馻r.morphological, histological and physiopathological indices of airway remodelling were detected. Secondl~to find out the relationship of TGF- P with airway remodelling,the expression of TGF- P in the models of airway remodelling and the changes of lung fibroblast in proliferation.differentiation and secretion regulation of collagen protein were studied.Finall~~experimental prevention and therapy with glucocorticosteroid and the traditional Chinese medicine Salvia Multiorrhiza 4 were observed and the possible mechanism were discussed. The main results and conclusion showed as below: 1. The models were producted by chronic exprosure with smoke by burning cigarette slowly in mice and with inhaltion of ovalbumin in sensitized guuinea pigs for 8 weeks.Detection with cellular,morphological, histological and physiopathological indices confirmed the models had the changes of airway remodelling model such as proliferation of airway smooth muscle cells,thickening of subepithelium and depositing of extracellular matrix.And these changes also led to respiratory dysfunction in the two models,which was characterised by oxygen delivery problem and airflow obstruction. 2. There were also different characters in the two models that were in the aspect of the airav%y inflammation, neutrophilic granulocyte mainly migrated and small airway or alveolar interval was damaged in COPD model;correspondingly lymphocytes and eosinophils infiltrated differentially and big air tract was injured in chronic asthmatic model. 3. The expression of TGF- P 1 in COPD or asthma models was increased tha that in control groups and was very significantly correlated with the content of lung collegan protein. 4. In vitro,it was found primary culture lung Iibroblast had no effect on proliferation after stimulating separately with TGF- P .Nevertheless,TGF- P could obviously promote the...
Keywords/Search Tags:Airway remodelling.TGF- β, CollagenAstbma, Lung fibroblast.Apoptsis, Chronic obstructive pulmonary disease, Cell culture, Glucocorticosteroid, Hybridization in situ.Salvia Multiorrhiza
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